Raikwar Geetanjali, Sharma Soumya, Kumar Dharmender, Mohan Sumedha, Dahiya Praveen
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida Sector-125, Uttar Pradesh, 201303, India.
Department of Biotechnology, Deenbandhu Chhotu Ram University of Science &Technology Murthal, Sonipat, Haryana, 131309, India.
Microb Pathog. 2025 Jun;203:107484. doi: 10.1016/j.micpath.2025.107484. Epub 2025 Mar 15.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of infections worldwide, and remains challenging due to its resistance mechanisms. This study investigated potential synergistic antimicrobial activity of essential oils from Piper betle (PBEO) and Anethum graveolens (AGEO) in combination with conventional antibiotics against MRSA. Molecular docking simulations (MDS) were performed to explore the interactions with key components of essential oils and target protein Penicillin-Binding Protein 2a (PBP2a), which contributes to antibiotic resistance. Synergistic antibacterial effects were evaluated using clinical MRSA isolates and a reference strain, through broth microdilution, checkerboard, and time-kill assays. Amongst all the combinations tested, antibiotic tetracycline exhibited synergistic (FICI <0.5) and additive (FICI >0.5 < 1) interactions for both essential oils. Time-kill confirmed essential oil-antibiotics enhanced anti-MRSA activity when compared to their individual effects over 24 h. MDS showed strong interactions with major components of PBEO and the allosteric site of PBP2a, when compared to the components of AGEO. In silico findings from the study showed molecular interactions underlying the antimicrobial effects, supporting experimental data and highlighting PBEO and AGEO with tetracycline as promising anti-MRSA therapeutic candidates.
耐甲氧西林金黄色葡萄球菌（MRSA）是全球感染的主要原因，由于其耐药机制，仍然具有挑战性。本研究调查了蒌叶精油（PBEO）和莳萝精油（AGEO）与传统抗生素联合使用对MRSA的潜在协同抗菌活性。进行了分子对接模拟（MDS），以探索精油关键成分与导致抗生素耐药性的靶蛋白青霉素结合蛋白2a（PBP2a）之间的相互作用。通过肉汤微量稀释法、棋盘法和时间杀菌试验，使用临床MRSA分离株和参考菌株评估协同抗菌效果。在所有测试的组合中，抗生素四环素对两种精油均表现出协同作用（FICI<0.5）和相加作用（FICI>0.5<1）。时间杀菌试验证实，与它们各自在24小时内的作用相比，精油-抗生素联合使用增强了抗MRSA活性。与AGEO的成分相比，MDS显示PBEO的主要成分与PBP2a的变构位点有强烈的相互作用。该研究的计算机模拟结果显示了抗菌作用背后的分子相互作用，支持了实验数据，并突出了PBEO、AGEO与四环素作为有前景的抗MRSA治疗候选药物。
